difluprednate ophthalmic (Rx)

Frequency Not Defined

Increased IOP

Anterior chamber inflammation

Corneal edema

Conjunctival edema

Blepharitis

Cataract

Optic nerve damage

Abnormal healing (after surgery)

Local irritation

Punctate keratitis

Hyperemia

Punctate keratitis

Decreased visual acuity

Eye pain

Photophobia

Postmarketing Reports

Elevated intraocular pressure

Posterior subcapsular cataract formation

Secondary ocular infection

Perforation of the globe

Contraindications

Most active viral diseases of cornea and conjunctiva including epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, and varicella, and also in mycobacterial infection of the eye and fungal diseases of ocular structures

Cautions

Not for intraocular administration

Prolonged use of corticosteroids may result in glaucoma with damage to optic nerve, defects in visual acuity and fields of vision; steroids should be used with caution in presence of glaucoma; monitor intraocular pressure if product used for ≥10 days

May increase risk of posterior subcapsular cataract formation

The use of steroids after cataract surgery may delay healing and increase incidence of bleb formation; perforations, associated with thinning of cornea or sclera, may occur; initial prescription and renewal of medication order beyond 28 days should be made by a physician only after examination of patient with aid of magnification such as slit lamp biomicroscopy and, where appropriate, fluorescein staining

Employment of corticosteroid medication in treatment of patients with history of herpes simplex requires great caution; use of ocular steroids may prolong course and may exacerbate severity of many viral infections of the eye (including herpes simplex)

Prolonged use of corticosteroids may suppress host response and thus increase hazard of secondary ocular infections; in acute purulent conditions, steroids may mask infection or enhance existing infection; if signs and symptoms fail to improve after 2 days, patient should be re-evaluated

Fungal infections of the cornea are particularly prone to develop coincidentally with long-term local steroid application; fungus invasion must be considered in any persistent corneal ulceration where steroid has been used or is in use; fungal culture should be taken when appropriate

The drug should not be instilled while wearing contact lenses; remove contact lenses prior to instillation; the preservative may be absorbed by soft contact lenses; lenses may be reinserted after 10 minutes following administration of this drug

Pregnancy

Shown to be embryotoxic (decrease in embryonic body weight and a delay in embryonic ossification) and teratogenic (cleft palate and skeletal anomalies) when administered subcutaneously to rabbits during organogenesis at a dose of 1-10 mcg/kg/day; the no- observed-effect-level (NOEL) for these effects was 1 mcg/kg/day, and 10 mcg/kg/day was considered to be a teratogenic dose that was concurrently found in the toxic dose range for fetuses and pregnant females

Treatment of rats with 10 mcg/kg/day subcutaneously during organogenesis did not result in any reproductive toxicity, nor was it maternally toxic; at 100 mcg/kg/day after subcutaneous administration in rats, there was a decrease in fetal weights and delay in ossification, and effects on weight gain in the pregnant females

It is difficult to extrapolate these doses of difluprednate to maximum daily human dose of this drug, since this drug is administered topically with minimal systemic absorption, and difluprednate blood levels were not measured in the reproductive animal studies; however, since use of this drug during human pregnancy has not been evaluated and cannot rule out the possibility of harm, this drug should be used during pregnancy only if potential benefit justifies potential risk to embryo or fetus

Lactation

It is not known whether topical ophthalmic administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in breast milk

Systemically administered corticosteroids appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects

Exercise caution when therapy administered to a nursing woman

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Antiinflammatory corticosteroid; inhibits inflammatory response including capillary dilation, edema, leukocyte migration, and scar formation

Absorption

Absorption: Negligible absorption

Metabolism: Undergoes deacetylation to active metabolite